Arterial Hypertension 动脉高血压
Arterial hypertension: Elevation of systolic and/or diastolic BP, either primary or secondary.
收缩压和/或舒张压的升高,为原发性或继发性。
Prevalence
患病率
It is estimated that there are nearly 50 million hypertensives in the USA (systolic BP >= 140 mm Hg and/or diastolic >= 90 mm Hg, or taking antihypertensive medication). For unknown reasons, the prevalence of hypertension seems to be decreasing in the USA. Hypertension occurs more often in black adults (32%) than in white (23%) or Mexican American (23%) adults, and morbidity and mortality are greater in blacks. Diastolic BP increases with age until age 55 or 60. form www.med66.com
据估计，美国有近5000万高血压患者(收缩压≥140mmHg和/或舒张压≥90mmHg,或服用抗高血压药物)。目前，美国高血压患病率似在降低，原因尚不清楚。黑人成人中的高血压发病(32%)率常大于白人(23%)或美国墨西哥成年人(23%)，黑人的发病率和死亡率也较高。在55或60岁以前，舒张压会随年龄增长而增加。
Prevalence of isolated systolic hypertension (ISH-- >= 140 mm Hg systolic, 50% of black and white men and > 60% of women over age 65 have hypertension. ISH is more prevalent among women than men in both races. Prevalence data, derived mainly from large screening programs such as the National Health and Nutrition Examination Survey, rely on one or more BP determinations made during one visit. Thus, these percentages are higher than they would be if BP had been measured over time (regression toward the mean). Between 85 and 90% of cases are primary (essential); in 5 or 10%, hypertension is secondary to bilateral renal parenchymal disease, and only 1 or 2% of cases are due to a potentially curable condition.
至少在80岁以前，单纯收缩期高血压(ISH-收缩压≥140mmHg,舒张压＜90mmHg)的患病率也随年龄而增加。如果将舒张性高血压和ISH患者考虑进去，那么，在65岁以上人群中，有50%以上的黑人和白人男性及60%以上的女性都有高血压。在这两个种族中，女性的ISH患病率高于男性。流行病学资料主要是从大规模筛查中获得的，如国家健康和营养情况调查等，它主要取决于一次调查中的单次或多次血压检测。因此，如果血压检测时间加长的话(降至均值)，这个百分比会更高。85%~90%的病例属原发性。5%或10%的高血压则是继发于两侧肾实质疾病，只有1%或2%的病例是由某个潜在的可治愈疾病所引起的。
Etiology and Pathogenesis
病因学和发病机制
Primary hypertension: Primary (essential) hypertension is of unknown etiology; its diverse hemodynamic and pathophysiologic derangements are unlikely to result from a single cause. Heredity is a predisposing factor, but the exact mechanism is unclear. Environmental factors (eg, dietary Na, obesity, stress) seem to act only in genetically susceptible persons. Isolated, perfused kidneys from Dahl salt-sensitive rats (which are genetically prone to hypertension when fed a high-salt diet) do not excrete water or Na as rapidly as those from Dahl salt-resistant rats, even before hypertension develops.
原发性高血压 原发性高血压的病因学尚不清楚；其多种血液动力学和病理生理学改变决非单一病因所致。遗传是患病因素之一，但确切的机制并不清楚。环境因素（如饮食中钠的含量、肥胖症、紧张等）似乎也只是对基因易感者有作用。即使在发生高血压之前，来自于Dahl盐敏感鼠的游离灌注肾（遗传性地在喂饲高盐饮食产生高血压）的不或钠排泄也没有Dahl盐抵抗鼠那么快。
The pathogenic mechanisms must lead to increased total peripheral vascular resistance (TPR) by inducing vasoconstriction, to increased cardiac output (CO), or to both because BP equals CO (flow) times resistance. Although expansion of intravascular and extravascular fluid volume is widely claimed to be important, such expansion can only raise BP by increasing CO (by increasing venous return to the heart), by increasing TPR (by causing vasoconstriction), or by both; it frequently does neither.
由于诱发血管收缩，致病机制肯定要导致周围血管总阻力（TPR）或心排血量（CO）的增加，或两者兼而有之，因为血压等于心排血量(血流)和阻力的乘积。虽然普遍认为血管内和血管外液体容量的扩张很重要，但这种扩张只会通过增加CO（通过增加静脉回心血量）或TPR（通过导致血管收缩）或是两者来升高血压。这两种情况往往都不会出现。
Abnormal Na transport across the cell wall due to a defect in or inhibition of the Na-K pump (Na+,K+-ATPase) or due to increased permeability to Na+ has been described in some cases of hypertension. The net result is increased intracellular Na, which makes the cell more sensitive to sympathetic stimulation. Because Ca follows Na, it is postulated that the accumulation of intracellular Ca (and not Na per se) is responsible for the increased sensitivity. Na+,K+-ATPase may also be responsible for pumping norepinephrine back into the sympathetic neurons to inactivate this neurotransmitter. Thus, inhibition of this mechanism could conceivably enhance the effect of norepinephrine. Defects in Na transport have been described in normotensive children of hypertensive parents.
由于钠-钾泵（Na+ ,K+ -ATP酶）的缺陷或抑制，或是由于对钠通透性的增高，导致跨细胞壁钠转运异常，这种情况已在一些高血压病例中加以阐述。它的最终结果是细胞内钠的增加，使细胞对交感神经的刺激更加敏感。因为钙随钠转运，有人推测细胞内钙的蓄积(而不是钠本身)对敏感性的增加负有责任。钠、钾、ATP酶对去甲肾上腺素泵回交感神经元灭活这神经递质也有责任。因此可以想象，抑制这种机制可以增强去甲肾上腺素的作用。我们已在双亲患高血压而儿童血压正常部分对钠转运缺陷进行了阐述。
Stimulation of the sympathetic nervous system raises BP, usually more in hypertensive or prehypertensive patients than in normotensive patients. Whether this hyperresponsiveness resides in the sympathetic nervous system itself or in the myocardium and vascular smooth muscle that it innervates is unknown, but it can often be detected before sustained hypertension develops. A high resting pulse rate, which can be a manifestation of increased sympathetic nervous activity, is a well-known predictor of subsequent hypertension. Some hypertensive patients have a higher-than-normal circulating plasma catecholamine level at rest, especially early in clinical development.
交感神经系统刺激升高血压，这种情况在高血压或高血压前期病人中通常比正常血压病人更多见。这种高反应性是存在于交感神经系统本身还是存在于受神经支配的心肌和血管平滑肌尚不清楚，但是，在持续性高血压发生之前常常可以发现这种高反应性。静息脉率加快可能是交感神经活动增强的表示，它也是众所周知的高血压先兆。一些高血压病人休息时的循环血浆儿茶酚胺值高于正常，尤其是在临床发病早期。
Drugs that depress sympathetic nervous activity frequently reduce BP in patients with primary hypertension. However, this observation cannot be considered evidence for implicating the sympathetic nervous system as the causative factor in primary hypertension. In hypertensive patients, the baroreflexes tend to sustain rather than counteract hypertension, a phenomenon known as "resetting the barostats," which may be a result rather than a cause of hypertension. Some hypertensive patients have defective storage of norepinephrine, thus permitting more to circulate.
抑制交感神经活性的药物可以降低原发性高血压病人的血压。然而，并不能将其看作是交感神经系统为原发性高血压诱因的证据。在高血压病人中，压力反射往往是维持而不是抵消高血压，也就是人们所说的“压力调节器复位”现象，它可能是高血压的结果，而不是原因。有些高血压病人存在去甲肾上腺素贮存缺陷，造成较多的去甲肾上腺素进入循环。
In the renin-angiotensin-aldosterone system, the juxtaglomerular apparatus helps regulate volume and pressure. Renin, a proteolytic enzyme formed in the granules of the juxtaglomerular apparatus cells, catalyzes conversion of the protein angiotensinogen to angiotensin I, a decapeptide. This inactive product is cleaved by a converting enzyme, mainly in the lung but also in the kidney and brain, to an octapeptide, angiotensin II, which is a potent vasoconstrictor that also stimulates release of aldosterone. Also found in the circulation, the des-ASP heptapeptide (angiotensin III) is as active as angiotensin II in stimulating aldosterone release but has much less pressor activity.
在肾素-血管紧张素-醛固酮系统中，肾小球旁体帮助调节血容量和压力。肾素是肾小球旁体细胞颗粒内形成的一种蛋白水解酶，催化蛋白血管紧张素原转换为血管紧张素Ⅰ，即十肽。这一非活性产物经转换酶裂解，主要是在肺部但也在肾和脑部，成为八肽，即血管紧张素Ⅱ，这是和中强烈的血管收缩素，可刺激醛固酮的释放。同样可以在血循环中发现的去天门冬氨酸七肽（血管紧张素Ⅲ），它在刺激醛固酮释放时的作用与血管紧张素Ⅱ一样，但其升压作用则不如后者。
Renin secretion is controlled by at least four mechanisms that are not mutually exclusive: A renal vascular receptor responds to changes in tension in the afferent arteriolar wall; a macula densa receptor detects changes in the delivery rate or concentration of NaCl in the distal tubule; circulating angiotensin has a negative feedback effect on renin secretion; and the sympathetic nervous system stimulates renin secretion via the renal nerve mediated by β receptors.
肾素的分泌至少受四种互不排斥的机制控制：肾血管受体对向心小动脉壁张力变化的反应；致密斑受体发现远端肾小管内氯化钠传递速率或浓度的变化；循环的血管紧张素对肾素的分泌的负反馈效应；和交感神经系统经由β受体介导的肾神经刺激分泌肾素。
Plasma renin activity (PRA) is usually normal in patients with primary hypertension but is suppressed in about 25% and elevated in about 15%. Hypertension is more likely to be accompanied by low renin levels in blacks and the elderly. The accelerated (malignant) phase of hypertension is usually accompanied by elevated PRA. Although angiotensin is generally acknowledged to be responsible for renovascular hypertension, at least in the early phase, there is no consensus regarding the role of the renin-angiotensin-aldosterone system in patients with primary hypertension, even in those with high PRA.
原发性高血压病人的血浆肾素活性(PRA)通常是正常的，但约25%受抑制，约15%可能升高。在黑人和老年高血压患者中，更可能伴有低肾素水平。高血压急进（恶性）期多伴有PRA增高。普遍认为，血管紧张素对肾血管性高血压负有责任，至少是在早期，但是，在原发性高血压病人，甚至是PRA升高的原发性高血压病人中，人们对肾素-血管紧张素-醛固酮系统所起的作用尚无一致意见。
The mosaic theory states that multiple factors sustain elevated BP even though an aberration of only one was initially responsible; eg, the interaction between the sympathetic nervous system and the renin-angiotensin-aldosterone system. Sympathetic innervation of the juxtaglomerular apparatus in the kidney releases renin; angiotensin stimulates autonomic centers in the brain to increase sympathetic discharge. Angiotensin also stimulates production of aldosterone, which leads to Na retention; excessive intracellular Na enhances the reactivity of vascular smooth muscle to sympathetic stimulation.
镶嵌理论认为，有多种因素使血压维持在升高位置，尽管最初起作用的异常因素只有一个，如交感神经系统和肾素-血管紧张素-醛固酮之间的相互作用。肾脏肾小球旁体的交感神经支配释放肾素；血管紧张素刺激大脑自主中枢，增加交感冲动发放。它还刺激醛固酮的产生，导致钠潴留；细胞内钠过多增强血管平滑肌对交感刺激的反应性。
Hypertension leads to more hypertension. Other mechanisms become involved when hypertension due to an identifiable cause (eg, catecholamine release from a pheochromocytoma, renin and angiotensin from renal artery stenosis, aldosterone from an adrenal cortical adenoma) has existed for some time. Smooth muscle cell hypertrophy and hyperplasia in the arterioles resulting from prolonged hypertension reduce the caliber of the lumen, thus increasing TPR. In addition, trivial shortening of hypertrophied smooth muscle in the thickened wall of an arteriole will reduce the radius of an already narrowed lumen to a much greater extent than if the muscle and lumen were normal. This may be why the longer hypertension has existed, the less likely surgery for secondary causes will restore BP to normal.
高血压引起更多的高血压病。当因某些易于确定的原因所引起的高血压存在一段时间后，如嗜铬细胞瘤释放的儿茶酚胺、肾动脉狭窄所产生的肾素和血管紧张素、肾上腺皮质腺瘤分泌的醛固酮等，其他机制也会参与高血压病的形成。长期高血压引起小动脉平滑肌细胞肥大和增生，使管腔口径变小，从而增加TPR。另外，小动脉壁增厚时，肥大的平滑肌细胞有轻微缩短，从而使业已狭窄的管腔半径比肌肉和管腔正常时更为缩小。这可能就是为什么高血压时间越长、继发性高血压手术使血压恢复正常的可能性越小的原因。
Deficiency of a vasodilator substance rather than excess of a vasoconstrictor (eg, angiotensin, norepinephrine) may cause hypertension. The kallikrein system, which produces the potent vasodilator bradykinin, is beginning to be studied. Extracts of renal medulla contain vasodilators, including a neutral lipid and a prostaglandin; absence of these vasodilators due to renal parenchymal disease or bilateral nephrectomy would permit BP to rise. Modest hypertension sensitive to Na and water balance is characteristic in anephric persons (renoprival hypertension).
高血压也可能是由血管扩张物质的缺乏而引起，并不是因为血管收缩物质的过剩，如血管紧张素、去甲肾上腺素。血管舒缓素系统产生强力的血管扩张物质缓激肽，有人正开始这种研究。肾脏髓质提取物中含有血管扩张物质，包括一种中性脂质和一种前列腺素。因肾实质疾病或双侧肾切除术造成这些血管扩张物质缺乏，可能会使血压升高。对钠和水平衡敏感的中度高血压是无肾脏者的特征（肾功能缺乏性高血压）。
Endothelial cells produce potent vasodilators (nitric oxide, prostacyclin) and the most potent vasoconstrictor, endothelin. Therefore, dysfunction of the endothelium could have a profound effect on BP. The endothelium's role in hypertension is being investigated. Evidence that hypertensive persons have decreased activity of nitric oxide is preliminary.
内皮细胞产生强烈的血管扩张素（一氧化氮、前列环素）和最强烈的血管收缩素――内皮素。因此，内皮细胞功能不全可能会对血压产生深远影响。人们正在研究内皮细胞在高血压中的作用，并已经初步发现高血压者一氧化氮活性降低的证据。
